This proposal will focus on the metaplasia of ocular epithelium in response to extracellular stimuli. During retinal detachment and proliferative vitreoretinopathy, retinal pigment epithelium (RPE) undergoes a metaplasia which contributes to the progression of the pathology. The research proposal will study two aspects of this metaplasia. First, we will study the expression of a class of genes, the proto-oncogenes, which play key roles in control of proliferation and differentiation. To accomplish this goal we will measure the expression of RNA complementary to various proto-oncogenes. This will be done in RPE cells whose proliferative and differentiated phenotypes have been experimentally altered to mimic in vivo conditions. Understanding the factors which control expression of these genes will give us insight into their function and how they might be manipulated to control metaplasia. Second, we will study the control of cellular functions which are characteristic of the cell's differentiated phenotype. In RPE cells we will study the control of extracellular lysosomal enzymes. We will measure the levels of extracellular lysosomal enzymes in response to stimuli which mimic in vivo pathological events, such as retinal detachment, or stimuli which are present under physiologically normal conditions. Our goal is to understand the mechanism of control of extracellular lysosomal enzymes under these conditions. We will also study the metaplasia of conjunctival epithelium (CE) to corneal-like epithelium which follows a total loss of corneal epithelium, a condition which occurs following acid and alkali burns. We will study the control of metabolism of arachidonic acid to 12-HETE since this capacity is a characteristic of conjunctival epithelium and it is retained in metaplasic CE; and ultimately what role this plays in healing and subsequent response to inflammatory stimuli.